Oxidative stress induces extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase in cystic fibrosis lung epithelial cells: Potential mechanism for excessive IL-8 expression

2008 ◽  
Vol 40 (3) ◽  
pp. 432-446 ◽  
Author(s):  
Emilie Boncoeur ◽  
Vinciane Saint Criq ◽  
Elise Bonvin ◽  
Telma Roque ◽  
Alexandra Henrion-Caude ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Protein Kinase ◽  
Lung Epithelial Cells ◽  
Mitogen Activated Protein Kinase ◽  
Potential Mechanism ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Lung Epithelial ◽  
Mitogen Activated Protein

scholarly journals Extracellular Signal-regulated Kinase Mediates Phosphorylation of Tropomyosin-1 to Promote Cytoskeleton Remodeling in Response to Oxidative Stress: Impact on Membrane Blebbing

2003 ◽  
Vol 14 (4) ◽  
pp. 1418-1432 ◽  
Author(s):  
François Houle ◽  
Simon Rousseau ◽  
Nick Morrice ◽  
Mario Luc ◽  
Sébastien Mongrain ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Focal Adhesions ◽  
Mitogen Activated Protein Kinase ◽  
Stress Fibers ◽  
Cell Contractility ◽  
Extracellular Signal Regulated Kinase ◽  
Membrane Blebbing ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Oxidative stress induces in endothelial cells a quick and transient coactivation of both stress-activated protein kinase-2/p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases. We found that inhibiting the ERK pathway resulted, within 5 min of oxidative stress, in a misassembly of focal adhesions characterized by mislocalization of key proteins such as paxillin. The focal adhesion misassembly that followed ERK inhibition with the mitogen-activated protein kinase kinase (MEK) inhibitor PD098059 (2′-amino-3′-methoxyflavone) or with a kinase negative mutant of ERK in the presence of H2O2resulted in a quick and intense membrane blebbing that was associated with important damage to the endothelium. We isolated by two-dimensional gel electrophoresis a PD098059-sensitive phosphoprotein of 38 kDa that we identified, by mass spectrometry, as tropomyosin-1. In fact, H2O2 induced a time-dependent phosphorylation of tropomyosin that was sensitive to inhibition by PD098059 and UO126 (1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butanediane). Tropomyosin phosphorylation was also induced by expression of a constitutively activated form of MEK1 (MEKCA), which confirms that its phosphorylation resulted from the activation of ERK. In unstimulated cells, tropomyosin-1 was found diffuse in the cells, whereas it quickly colocalized with actin and stress fibers upon stimulation of ERK by H2O2 or by expression of MEKCA. We propose that phosphorylation of tropomyosin-1 downstream of ERK by contributing to formation of actin filaments increases cellular contractility and promotes the formation of focal adhesions. Incidentally, ML-7 (1-[5iodonaphthalene-1-sulfonyl]homopiperazine, HCl), an inhibitor of cell contractility, inhibited phosphorylation of tropomyosin and blocked the formation of stress fibers and focal adhesions, which also led to membrane blebbing in the presence of oxidative stress. Our finding that tropomyosin-1 is phosphorylated downstream of ERK, an event that modulates its interaction with actin, may lead to further understanding of the role of this protein in regulating cellular functions associated with cytoskeletal remodeling.

MEK5/ERK5: Mitogen-Activated Protein Kinase 5/Extracellular Signal-Regulated Kinase 5

2012 ◽  
pp. 1074-1074
Author(s):  
Andreas Gewies ◽  
Jürgen Ruland ◽  
Alexey Kotlyarov ◽  
Matthias Gaestel ◽  
Shiri Procaccia ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein
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